PROSPECTIVE VALIDATION OF HIGH-SHEAR WET GRANULATION PROCESS BY WET GRANULE SIEVING METHOD .2. UTILITY OF WET GRANULE SIEVING METHOD

The general utility of a method for determination of high-shear wet gr anulation end point by monitoring the wet granule particle size distri bution was evaluated. Wet granulation was conducted in a 25-liter high -shear mixer using four model drugs with different solubilities and pa rticle sizes (ethenzamide, unmilled and milled acetaminophen, and anti pyrine). For each drug formulation, its wet granule particle size frac tion and target range for granulation end point determination were sel ected based on the tablet characteristics that are known to be influen ced by the wet granulation process. Granules manufactured under differ ent conditions (i.e., different main and chopper blade speeds and bind er supplying rate) but manufactured to the same granulation end point determined by the selected fraction and range showed very similar gran ule characteristics and subsequently very similar tablet characteristi cs. From the fact that there was a good correlation between the wet an d dry-sized granule particle size distributions even if the drying met hod was changed from fluid-bed drying to vacuum drying, the general ap plication of the end point determining method was verified. Further, t he method was shown to be sensitive to the critical granulation parame ters for granulation progression and to be very capable of determining the granulation extent. Thus, it was suggested that the method is app licable to various drugs and formulations for determination of wet gra nulation end point.